title: Effect of NADPH oxidase inhibition on the expression of kidney injury molecule and calcium oxalate crystal deposition in hydroxy-L-proline-induced hyperoxaluria in the male Sprague-Dawley rats.
abstract: BACKGROUND
  Renal calcium oxalate (CaOx) crystal deposition is associated with epithelial injury and movement of inflammatory cells into the interstitium. We have proposed that oxalate (Ox)- and CaOx crystal-induced injury is most likely caused by reactive oxygen species (ROS) produced by activation of membrane nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
  
  
  METHODS
  Present study was undertaken to determine the effect of NADPH oxidase inhibitor apocynin on the expression of kidney injury molecule-1 (KIM-1) and renal CaOx crystal deposition in rats with hyperoxaluria. We also investigated the urinary excretion of KIM-1, osteopontin (OPN) and monocyte chemoattractant protein-1 (MCP-1) and renal expression of OPN and ED-1. Male Sprague-Dawley rats were fed a diet containing 5% hydroxyl-L-proline (HLP) and 4 mmol apocynin to drink for 28 days. Urine was collected on Days 7, 14, 21 and 28. After that, rats were sacrificed and their kidneys processed for various microscopic and molecular investigations.
  
  
  RESULTS
  HLP consumption produced heavy deposits of CaOx crystals. Renal expression of KIM-1 and OPN and urinary excretion of KIM-1, OPN, H(2)O(2) and MCP-1 was significantly increased. ED-1-positive cells migrated into renal interstitium. Apocynin treatment caused significant reduction of crystal deposits, injured and dilated tubules; renal expression of KIM-1, OPN and ED-1 and urinary excretion of KIM-1, OPN, MCP-1 and H(2)O(2). Apocynin had no effect on the urinary excretion of Ox.
  
  
  CONCLUSIONS
  This is the first study of urinary excretion and renal expression of KIM-1 in association with renal CaOx crystal deposition, experimental or clinical. The results indicate that NADPH oxidase inhibition leads to reduction in KIM-1 expression and urinary excretion as well as renal CaOx crystal deposition. KIM-1 is an important marker of renal epithelial injury. The results provide further support to our proposal that renal epithelial injury is critical for crystal retention and that injury is in part caused by the production of ROS with the involvement of NADPH oxidase.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.forename: Aslam
authors.initials: A
authors.lastname: Khan
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Glenton
authors.forename: Saeed R
authors.initials: SR
authors.lastname: Khan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002129:Calcium Oxalate / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D006909:Hydroxyproline / Q000633:toxicity*; D006959:Hyperoxaluria / Q000139:chemically induced* / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D010070:Oxalates / Q000494:pharmacology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002129:Calcium Oxalate; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D006909:Hydroxyproline; D019255:NADPH Oxidases; D053495:Osteopontin; D010070:Oxalates; D017382:Reactive Oxygen Species; C110936:Havcr1 protein, rat